The Animal Models Core (AMC) will support all of the research projects in the program by providing the necessary genetically modified mice and producing low-passage in vivo human gastro-intestinal cancer explants in mice. One mission of the AMC will be to maintain mice for long-term studies to evaluate predisposition to cancer. A second mission of the AMC will be maintaining stocks of the genetically modified strains (e.g., elf, eif/Smad4, Smad4, Smad3, Cdk4-R24C mutant, cdk4 null mutant, htert knockout), and to breed these strains together to produce fetuses of double and triple mutant homozygous genotypes. Working with the Tissue Core B, these fetuses will be used as a source of embryonic fibroblasts and tumor cells by the projects. Pups with the desired double or triple mutant genotypes will constitute a large fraction of the progeny. To provide a continuous supply in support of the research projects a large amount of breeding, coupled with genotype analysis to identify the appropriate individuals will be required. A third mission of the AMC will be to provide synergy between the clinicians and projects testing anti-cancer drug therapies. This synergy will be in the form of producing, and providing husbandry of mice harboring genetic backgrounds predisposed to making tumors or nude mice xenografted with human tumor tissues for propagating lowpassage tumors. All mice will be produced and housed under barrier conditions that ensure continuing specific pathogen free status, Centralization of the production and care of these mice under the AMC will limit the number of individuals handling the animals, thereby further safeguarding their health. Moreover, by centralizing the production and dispensation of these genetically valuable animals, the animal core will be able to coordinate usage among the different projects, avoid wastage, and achieve an economy of scale that will permit these studies to be completed at less expense than if undertaken separately. A final mission of the AMC will be to serve as a synergistic hub for all projects and cores.